Fig. 4. Comparison of the structures of class A muscarinic M₂R, class B Glucagon GCGR, and class C metabotropic glutamate mGlu₂R in complex with Gi or arrestin-2.

The structure of inactive M₂R (PDB: 3UON) [88] is superposed with activated M₂R in complex with Go_A (panel A, PDB: 6OIK) [40] and arrestin-2 (panel B, PDB: 6U1N) [46]. The structure of inactive GCGR (PDB: 5YQZ) [87] is superposed with activated GCGR in complex with Gi₁ (panel C, PDB: 6LML) [42]. The structure of inactive mGlu₂R (PDB: 7MTQ) [44] is superposed with activated mGlu₂R in complex with Gi₁ (panel D, PDB: 7MTS) [44]. Shown are side views (left panels), and schematic representation of helices from extracellular (middle panels) and cytoplasmic views (right panel). The positions of helices in the inactive state are shown in light blue, active in red. Inactive receptors are colored purple in left panels. The residues of the active receptor in complex with intracellular partners are color coded based on the RMSD of α-carbons from the matched residues in the inactive receptor with thresholds of 2.5 Å (cyan), 5 Å (green), 7.5 Å (yellow), 10 Å (orange), and 12.5 Å (red). The direction and extent of displacement of helices are also indicated by arrows.